December 15, 2022
PAR-21-237 - NINDS Efficacy Clinical Trials (UG3/UH3 Clinical Trial Required)
National Institute of Neurological Disorders and Stroke (NINDS)
This Notice of Special Interest is to advise the research community of NINDS interest in clinical trials to study epidural stimulation in spinal cord injury that meet the requirements of PAR-21-237 NINDS Efficacy Clinical Trials (UG3/UH3 Clinical Trial Required) Funding Opportunity Announcement.
The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease for all people. Spinal Cord Injury (SCI) can occur following an acute or long-term insult to the spinal cord, resulting in devastating neurological loss and concomitant systemic dysfunction with no current ameliorative treatment or cure. The most recent estimate of the incidence of traumatic SCI in the United States indicates an additional 18,000 new acute SCI cases each year, with an estimated prevalence of 300,000 individuals in the US currently living with SCI1.
Although regeneration and repair of the injured spinal cord is not currently possible, since 2011 clinical studies of electrical stimulation of the spinal cord (spinal cord epidural stimulation, scES) have provided proof of principle that some recovery of motor function is possible even after the most severe injury. Since 2018 additional research has suggested that scES can also result in restoration of essential autonomic functions. Preclinical research has clarified some of the neurological mechanisms involved, while exploratory and mechanistic clinical trials in small patient numbers (in the range of 1-10 participants) report that scES can improve health and quality of life for individuals with chronic SCI through the restoration of a range of functional outcomes including improved motor function, bowel and bladder control, and hemodynamic regulation.
In February 2019 the NIH hosted the conference SCI 2020: Launching a Decade for Disruption in Spinal Cord Injury Research2, proceedings from this meeting were published in April 20213. Neuromodulation, including scES, to improve neurological function, was one of the top scientific domains identified as a priority by persons with lived experience with SCI and the research community. Discussion points included recommendations that neuromodulation therapies deliver outcomes that enable everyday living and preserve health and well-being for the future and could include approaches targeting respiratory, urinary, musculoskeletal, and cardiovascular systems. At more recent meetings of the SCI research and public stakeholder communities, investigators have continued to report results from small exploratory clinical trials and have built the body of evidence to the point where community members have expressed confidence that the field is ready for an efficacy study, described in the medical device field as a Pivotal study, of the use of scES for recovery after SCI. A medical device Pivotal study is a definitive study in which evidence is gathered to support the safety and effectiveness evaluation of the medical device for its intended use. Evidence from one or more Pivotal clinical studies generally serves as the primary basis for the determination of reasonable assurance of safety and effectiveness of the medical device of a Pre-Market Approval application (PMA) from the FDA.
The FDA provides guidance for such studies, as described in the Objectives, below. In all cases the investigators need to work closely with the FDA to ensure the designed study does meet the requirements for a Pivotal study.
Investigators studying epidural stimulation where the research is not ready for a well-designed Pivotal study should reach out to the contact PO for advice on other appropriate funding opportunities such as Pilot/Early Feasibility or mechanistic clinical trials.
1 National Spinal Cord Injury Statistical Center, Traumatic Spinal Cord Injury Facts and Figures at a Glance. Birmingham, AL: University of Alabama at Birmingham, 2022.
3Morse, L et al., Journal of Neurotrauma volume 38, Number 9, pp 1251-1266. DOI: 10.1089/neu.2020.7174
Application and Submission Information
This notice applies to the February 9 ,2023 receipt date and subsequent due dates through October 10, 2023.
Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
Linda Bambrick, PhD